Studies will be performed on cellular host defense mechanisms related to opportunistic infection. Investigation will concentrate on cryptococcosis as a model of such infections with special emphasis on killing of non- phagocytized organisms by lymphoid cells, a recently described antibody associated fungicidal mechanism. The relative importance of this and other fungicidal mechanisms in vivo will be studied. In vitro assays of killing of cryptococci by separated phagocytic and non-phagocytic cells will be performed. There will be two main avenues of approach to determine the importance of factors influencing the outcome of infection: (1) use of an experimental model of infection in the quinea pig; (2) studies of purified subpopulations of leucocytes obtained from human peripheral blood. Use of an animal model will permit study of those lymphoid cells which can kill cryptococci by non-phagocytic mechanism. The development and localization of these cells as well as the development of specific antibody during cryptococcal infection will be correlated with survival of animals. Finally, immunosuppression by corticosteroids and cyclophosphamide will be correlated with suppression of immunologic parameters including lymphoid cell fungicidal activity, as well as with duration of survival of animals. Human cells will be obtained from normal subjects as well as patients with Hodgkin's disease. Other patients receiving corticosteroid or other immunosuppressive therapy will also be evaluated. The patient group will be studied serially to correlate results with the course of illness and with therapy, as well as intercurrent mycotic infections. This will help to determine immunologic markers which correlate with fungicidal activity as well as the effect of immunosuppressive therapy and disease activity on fungicidal mechanisms in man.